Duplication of 8p23.2: A benign cytogenetic variant?

Abstract

We describe a duplication of the 8p23.2 band in seven individuals from four families. The duplication was recognizable as an enlarged 8p23.2 band on G-banded chromosomes at the 550 band level. It was transmitted from a parent to offspring in three of the four families in which both parents were karyotyped. Each proband in the four families had the enlarged band and showed various phenotypic abnormalities, but the abnormalities were inconsistent. Chromosomal and interphase fluorescence in situ hybridization (FISH) analysis of the enlarged band region defined a 2.5-Mb duplicated segment common to all seven individuals studied. Interphase FISH analysis of peripheral blood lymphocytes from 50 unrelated normal individuals showed the duplication in three individuals. In view of these findings, it is most likely that the 8p23.2 duplication we described is a normal variant.

Duplications and copy number variants of 8p23.1 are cytogenetically indistinguishable but distinct at the molecular level

“…Thirdly, overlapping duplications of 8p22 -p23.1 have been reported in patients with Kabuki syndrome 15 but these findings have not been replicated by others in clinically well characterised patients. 16 Fourthly, duplications of 8p23.1 -8p23.3 have been reported in normal individuals 17,18 and it is therefore possible that the clinical effect of the smaller triplication in family 1 is minimal. Many of these duplications include the GATA4 gene, deletions 19 and intragenic mutations of which give rise to heart disease.…”

Multiplex Ligation-Dependent Probe Amplification Analysis ofGATA4Gene Copy Number Variations in Patients with Isolated Congenital Heart Disease

“…Recently, an atypical small interstitial deletion of 8p23 that includes the GATA4 gene was also described in two unrelated patients showing Ebstein anomaly associated with septal defects [24]. Furthermore, duplications of GATA4 gene have been observed in normal as well as in syndromic patients with and without heart defects, suggesting that GATA4 is a dosage-sensitive gene with variable penetrance [25][26][27][28].…”

Expansion of a 12-kb VNTR containing the REXO1L1 gene cluster underlies the microscopically visible euchromatic variant of 8q21.2

“…Most of the EVs are clinically innocuous but the 8p23.1 EV has been associated with a number of traits [5][6][7][8] and the 4p16.1 EV co-segregated with microtia. 4 EVs need to be distinguished from pathological imbalances with which they may be similar or even identical under the light microscope. 5,19,21,24,25 Recently, Manvelyan et al 9 reported three patients of Middle European and Japanese descent with a microscopically visible CNV of 8q21.2.…”